Efficacy, Safety and Tolerability of PF-06649751 in Parkinson's Disease Patients With Motor Fluctuations
Sponsor
Pfizer (Industry)
Overall Status
Terminated
CT.gov ID
NCT02687542
Collaborator
(none)
108
57
5
20.3
1.9
0.1
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy, safety and tolerability of PF-06649751 in Parkinson's disease patients who experience motor-fluctuations.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
The study has a randomized, double-blind, placebo-controlled parallel group design. Approximately 198 subjects will be randomized to 5 treatment groups. Each subject will participate in the study for approximately 23 weeks including a 30 day screening period, 15 week double blind treatment period, and an approximately 28 day follow-up period.
Study Design
Study Type:
Interventional
Actual Enrollment
:
108 participants
Allocation:
Randomized
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A 15-WEEK, PHASE 2, DOUBLE BLIND, RANDOMIZED, PLACEBO-CONTROLLED, DOSE RANGING STUDY TO INVESTIGATE THE EFFICACY, SAFETY AND TOLERABILITY OF PF-06649751 IN SUBJECTS WITH MOTOR FLUCTUATIONS DUE TO PARKINSON'S DISEASE
Actual Study Start Date
:
Mar 3, 2016
Actual Primary Completion Date
:
Nov 10, 2017
Actual Study Completion Date
:
Nov 10, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Placebo |
Drug: Placebo
Placebo
|
| Experimental: PF-06649751 low dose (1 mg QD) PF-06649751 low dose level (1 mg QD) |
Drug: PF-06649751 low dose (1 mg QD)
PF-06649751 low dose (1 mg QD)
|
| Experimental: PF-06649751 middle dose 1 (3 mg QD) PF-06649751 lower middle dose 1 (3 mg QD) |
Drug: PF-06649751 middle dose 1 (3 mg QD)
PF-06649751 lower middle dose 1 (3 mg QD)
|
| Experimental: PF-06649751 middle dose 2 (7 mg QD) PF-06649751 higher middle dose 2 (7 mg QD) |
Drug: PF-06649751 middle dose 2 (7 mg QD)
PF-06649751higher middle dose 2 (7 mg QD)
|
| Experimental: PF-06649751 high dose (15 mg QD) PF-06649751 high dose (15 mg QD) |
Drug: PF-06649751 high dose (15 mg QD)
PF-06649751 high dose (15 mg QD)
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Daily OFF Time at Week 10 [Week 10; Baseline was defined as the average daily OFF time (using 3 Hauser patient diary days) prior to Day -1 (study derived day and equalled to nominal visit day 0).]
A paper Hauser diary was utilized to record motor state for half-hour intervals. Participants completed the diary by answering whether they had been OFF for 3 consecutive days in the week prior to each visit (except Day 28 visit), including 3 consecutive days during the week prior to Day 0 (Randomization). The daily OFF time was calculated as the average of the 3 consecutive daily OFF hours from the Hauser diary at each visit.
Secondary Outcome Measures
- Change From Baseline in Daily OFF Time [Weeks 3, 5, 10 and 15; Baseline was defined as the average daily OFF time (using 3 Hauser patient diary days) prior to Day -1 (study derived day and equalled to nominal visit day 0).]
A paper Hauser diary was utilized to record motor state for half hour intervals. Participants completed the diary by answering whether they had been OFF for 3 consecutive days in the week prior to each visit (except Day 28 visit), including 3 consecutive days during the week prior to Day 0 (Randomization). The daily OFF time was calculated as the average of the 3 consecutive daily OFF hours from the Hauser diary at each visit. Results at Week 15 should be interpreted with caution given almost half the participants were not available for this analysis at Week 15 as compared to Week 10 and the complicated nature of protocol changes that impacted the study design after Week 10.
- Change From Baseline in Daily ON Time With Troublesome Dyskinesia [Weeks 3, 5, 10 and 15; Baseline was defined as the average daily ON time with Troublesome Dyskinesia (using 3 Hauser patient diary Days) prior to Day -1 (study derived day and equalled to nominal visit Day 0).]
A paper Hauser diary was utilized to record motor state for half hour intervals. The participants answered the Hauser diary on whether they had been ON with troublesome dyskinesia. A diary day started with the interval 24:00-0:30 through 23:30-24:00 on each chronological day for 3 consecutive days. On the days recording the home diary, participants made an entry every 30 minutes during their normal waking time and upon awakening from time asleep. The daily ON hours was calculated as the average of the 3 consecutive daily ON hours from the Hauser diary at each visit. Results at Week 15 should be interpreted with caution given almost half the participants were not available for this analysis at Week 15 as compared to Week 10 and the complicated nature of protocol changes that impacted the study design after Week 10.
- Change From Baseline in Daily ON Time Without Troublesome Dyskinesia [Weeks 3, 5, 10 and 15; Baseline was defined as the average daily ON time without Troublesome Dyskinesia (using 3 Hauser patient diary days) prior to Day -1 (study derived day and equalled to nominal visit Day 0)]
A paper Hauser diary was utilized to record motor state for half hour intervals. The participants answered the Hauser diary on whether they had been ON without troublesome dyskinesia. A diary day started with the interval 24:00-0:30 through 23:30-24:00 on each chronological day for 3 consecutive days. On the days recording the home diary, participants made an entry every 30 minutes during their normal waking time and upon awakening from time asleep. The daily ON hours was calculated as the average of the 3 consecutive daily ON hours from the Hauser diary at each visit. Results at Week 15 should be interpreted with caution given almost half the participants were not available for this analysis at Week 15 as compared to Week 10 and the complicated nature of protocol changes that impacted the study design after Week 10.
- Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III [Weeks 1, 2, 3, 4, 5, 10 and 15; Baseline was defined as the Day -1 (study derived day and equalled to nominal visit Day 0) measurement]
MDS-UPDRS Part III assessed the motor signs of Parkinson's disease and was administered by the investigator. It was comprised of 33 sub-scores based on 18 items, several with right, left or other body distribution scores. Each question was anchored with 5 responses that were linked to commonly accepted clinical terms: 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. If more than 7 of the Part III items were missing, the score for that time point was missing, otherwise MDS-UPDRS Part III score was imputed as sum of the non-missing items*(total number of items)/ (number of items non-missing). The MDS-UPDRS Part III total score range is 0-132. Higher score indicated more severe motor signs of Parkinson's disease. Results at Week 15 should be interpreted with caution given almost half the participants were not available for this analysis at Week 15 as compared to Week 10 and the complicated nature of protocol changes that impacted the study design after Week 10.
- Change From Baseline in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II, IV, and Total Score [Weeks 5, 10 and 15; Baseline was defined as the Day -1 (study derived day and equalled to nominal visit Day 0) measurement]
Each question of Part I,II or IV with 5 responses was linked to the same clinical terms as Part III.The score was missing if more than 7 items were missing for a time point; otherwise Part I,II or IV score was imputed as sum of non-missing items*(total number of items)/(number of items non-missing).•PartI (Non-Motor Aspects of Experiences of Daily Living) assessed non-motor experiences of daily living using 13questions(Range:0-52).•PartII(Motor Aspects of Experiences of Daily Living) assessed motor experiences of daily living using 13questions(Range:0-52).•PartIV(Motor Complications) assessed motor complications,dyskinesias, and motor fluctuations using historical and objective information with 6questions(Range:0-24).•MDS-UPDRS Total Score:the sum of Parts I,II,III,and IV(Range:0-260).Higher score indicated more severe motor signs of Parkinson's disease.Week15's results were interpreted cautiously given almost half participants were not available for the analysis as compared to Week10
- Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality [Baseline (Day 0) to Week 17]
The safety laboratory tests including Hematology, Clinical Chemistry and Urinalysis were performed. Determination if there were any laboratory data abnormalities of potential clinical concern was based on Pfizer Data Standards. Incidence of laboratory test abnormalities (without regard to baseline abnormality) was summarized within each treatment group.
- Number of Participants With Vital Sign Results Meeting the Criteria for Categorical Summarization [Baseline (Day 0) to Week 17]
Vital Signs including blood pressure and pulse rate were measured. Vital signs were collected first while the participant was in the supine position and then in the standing position.
- Number of Participants With Electrocardiogram (ECG) Results Meeting the Criteria for Categorical Summarization [Baseline (Day 0) to Week 17]
The average of the triplicate readings of ECG data was collected at each assessment time. Number of participants with ECG results meeting the criteria for categorical summarization for time from the beginning of the P wave until the beginning of the QRS complex (PR Interval), time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS Duration), time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT Interval) and corrected QT (Fridericia correction) (QTcF Interval) were presented.
- Number of Participants With Suicidal Ideation Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) at Post-baseline Visits [Days 0 (Baseline), 7, 14, 21, 28, 35, 70, 77, 84, 91, 105 and 119]
The Columbia Suicide Severity Rating Scale (C-SSRS) was an interview based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS responses were mapped to the C-CASA. There were 3 key endpoints for suicidality data analysis and evaluation: Suicidal Behavior: A participant was said to have suicidal behavior if the participant had experienced completed suicide / suicide attempt / reparatory acts toward imminent suicidal behavior. Suicidal Ideation: Any observed suicidal ideation mapped to a single C-CASA category. Suicidal Behavior or Ideation (participants with new onset suicidality): A participant was considered to have a new onset of suicidality if the participant reported no ideation and no behavior at the baseline assessment and reported any behavior or ideation post-baseline. Data observed at screening was not considered in the definition of worsening.
- Change From Baseline in Total Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale (QUIP-RS) [Baseline (Day 0) and Weeks 5, 10 and 15]
The QUIP-RS was a brief, patient reported outcome measure designed to assess the severity of symptoms of Impulsive-Compulsive Disorders (ICDs) and related behaviors reported to occur in Parkinson's disease. The QUIP-RS assessed 7 disorders (Gambling, Sex, Buying, Eating, Hobbyism-punding [performing tasks and repeating activities] and Taking medications). If more than 5 items were missing, the total QUIP-RS score was set as missing; otherwise, the total QUIP-RS score was imputed as follows: sum of the non-missing item scores * (total number of items) / (number of items non-missing). The higher score indicated a greater level of the ICD. The total QUIP-RS score for all ICDs and related disorders combined ranges from 0 to 112.
- Total Physician Withdrawal Checklist (PWC-20) on Days 105 and 119, and Change From Day 105 to Day 119 [Days 105 and 119]
The PWC-20 is a physician completed, 20 item reliable and sensitive instrument for the assessment of discontinuation symptoms. The PWC-20 was collected after the completion of study treatment and also at the first visit of follow-up. The total PWC-20 score was the sum of 20 item scores and ranged from 0 to 60. If more than 5 items were missing, the total PWC-20 score was missing; otherwise, the total PWC-20 score was imputed as follows: sum of the non-missing items * (total number of items) / (number of items non-missing). The higher score indicated more frequent/severe symptoms.
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs and Deaths [Day 1 to follow-up (Week 19 visit)]
An AE was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not need necessarily to have a causal relationship with the treatment or usage. An SAE was any untoward medical occurrence at any dose that: Resulted in death; Was life threatening (immediate risk of death); Required inpatient hospitalization or prolongation of existing hospitalization; Resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); Resulted in congenital anomaly/birth defect.
Eligibility Criteria
Criteria
Ages Eligible for Study:
40 Years
to 85 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Females of non-childbearing potential and/or male subjects between the ages of 40 and 85 years, inclusive.
-
Clinical diagnosis of Parkinson's disease.
-
Able to refrain from any Parkinson's disease medication not permitted by the protocol.
Exclusion Criteria:
-
Female of childbearing potential
-
History or presence of atypical Parkinsonian syndrome.
-
History of surgical intervention for Parkinson's disease.
-
Severe acute or chronic medical or psychiatric condition or laboratory abnormality.
-
Any condition possibly affecting drug absorption.
-
Participation in other studies involving investigational drug(s), or treatment with any investigational drug within 30 days.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Xenoscience, Inc | Phoenix | Arizona | United States | 85004 |
| 2 | St Joseph's Hospital and Medical Center | Phoenix | Arizona | United States | 85013 |
| 3 | Arcadia Neurology Center | Arcadia | California | United States | 91006 |
| 4 | Faculty Physicians and Surgeons of Loma Linda University School of Medicine | Loma Linda | California | United States | 92354 |
| 5 | Hoag Memorial Hospital Presbyterian | Newport Beach | California | United States | 92658 |
| 6 | Hoag Memorial Hospital | Newport Beach | California | United States | 92663 |
| 7 | SC3 Research Group, Inc | Pasadena | California | United States | 91105 |
| 8 | Neurosearch-Torrance | Torrance | California | United States | 90505 |
| 9 | Associated Neurologists of Southern Connecticut, PC | Fairfield | Connecticut | United States | 06824 |
| 10 | Parkinson's Disease and Movement Disorders Center of Boca Raton | Boca Raton | Florida | United States | 33486 |
| 11 | University of Florida Center for Movement Disorders and Neurorestoration | Gainesville | Florida | United States | 32607 |
| 12 | Neurology Associates of Ormond Beach | Ormond Beach | Florida | United States | 32174 |
| 13 | University of South Florida | Tampa | Florida | United States | 33613 |
| 14 | Vero Beach Neurology and Research Institute | Vero Beach | Florida | United States | 32960 |
| 15 | Atlanta Center for Medical Research | Atlanta | Georgia | United States | 30331 |
| 16 | Rush University Medical Center | Chicago | Illinois | United States | 60612 |
| 17 | Indiana University Health Neuroscience Center | Indianapolis | Indiana | United States | 46202 |
| 18 | Brigham and Women's Hospital | Boston | Massachusetts | United States | 02115 |
| 19 | CRI Worldwide, LLC | Marlton | New Jersey | United States | 08053 |
| 20 | Dent Neurologic Institute | Amherst | New York | United States | 14226 |
| 21 | Dent Neurosciences Research Center ,Inc. DBA Dent Neurologic Institute | Amherst | New York | United States | 14226 |
| 22 | Dent Neurologic Institute | Orchard Park | New York | United States | 14127 |
| 23 | Duke University Medical center | Durham | North Carolina | United States | 27705 |
| 24 | Duke University/Duke Neurology/Department of Neurology | Durham | North Carolina | United States | 27705 |
| 25 | Wake Research Associates, LLC | Raleigh | North Carolina | United States | 27612 |
| 26 | Cleveland Clinic | Cleveland | Ohio | United States | 44195 |
| 27 | University of Toledo | Toledo | Ohio | United States | 43614 |
| 28 | The Movement Disorder Clinic of Oklahoma | Tulsa | Oklahoma | United States | 74136 |
| 29 | Abington Neurological Associates, Ltd. | Willow Grove | Pennsylvania | United States | 19090 |
| 30 | Rhode Island Hospital/ Brown University Medical School | Providence | Rhode Island | United States | 02903 |
| 31 | AS Clinical Research Consultants of North Texas, PLLC | Greenville | Texas | United States | 75401 |
| 32 | Baylor College of Medicine | Houston | Texas | United States | 77030 |
| 33 | Booth Gardner Parkinson's Care Center | Kirkland | Washington | United States | 98034 |
| 34 | Montreal Neurological Hospital Research Pharmacy | Montreal | Quebec | Canada | H3A 2B4 |
| 35 | Montreal Neurological Institute and Hospital | Montreal | Quebec | Canada | H3A 2B4 |
| 36 | CHU de Grenoble Alpes | Grenoble | France | 38043 Cedex 9 | |
| 37 | CHU de Grenoble Alpes | La Tronche | France | 38700 | |
| 38 | CHRU de Lille-Hopital Roger Salengro | Lille | France | 59037 cedex | |
| 39 | Hopital de la Timone APHM | Marseille | France | 13385 cedex 05 | |
| 40 | Hopital de La Timone | Marseille | France | 13385 cedex 05 | |
| 41 | Hopital La Pitie-Salpetriere | Paris | France | 75013 | |
| 42 | Universitaetsklinikum Freiburg | Freiburg | Baden-wuerttemberg | Germany | 79106 |
| 43 | St. Josef-Hospital GmbH | Bochum | Germany | 44791 | |
| 44 | Universitaetsklinikum Carl Gustav Carus Klinik und Poliklinik fur Neurologie | Dresden | Germany | 01307 | |
| 45 | Klinikum rechts der Isar der Technischen Universitaet Muenchen | Muenchen | Germany | 81675 | |
| 46 | Universitaetsklinik Ulm | Ulm | Germany | 89081 | |
| 47 | Asahikawa Medical center | Asahikawa | Hokkaido | Japan | 0708644 |
| 48 | Medical Corporation Abe Neurology Clinic | Morioka | Iwate | Japan | 020-0878 |
| 49 | Tazuke Kofukai Medical Research Institute Kitano Hospital | Kita-ku | Osaka | Japan | 530-8480 |
| 50 | Osaka University Hospital | Suita | Osaka | Japan | 565-0871 |
| 51 | Juntendo University Hospital | Bunkyo-ku | Tokyo | Japan | 113-8431 |
| 52 | Hospital Clinico Universitario | Santiago de Compostela | A Coruna | Spain | 15706 |
| 53 | Hospital Universitari de Bellvitge | Hospitalet de Llobregat | Barcelona | Spain | 08907 |
| 54 | Policlinica de Guipuzcoa | San Sebastian | Guipuzcoa | Spain | 20009 |
| 55 | Hospital Clinic i Provincial de Barcelona | Barcelona | Spain | 08036 | |
| 56 | Hospital Universitario de la Princesa | Madrid | Spain | 28006 | |
| 57 | Hospital Universitario y Politecnico la Fe | Valencia | Spain | 46026 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02687542
Other Study ID Numbers:
- B7601003
- 2015-004912-39
- A-ROSE PD
- A-ROSE
First Posted:
Feb 22, 2016
Last Update Posted:
Nov 23, 2020
Last Verified:
Oct 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo | PF-06649751 1 mg QD | PF-06649751 3 mg QD | PF-06649751 7 mg QD | PF-06649751 15 mg QD |
|---|---|---|---|---|---|
| Arm/Group Description | The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. |
| Period Title: Overall Study | |||||
| STARTED | 23 | 13 | 15 | 13 | 44 |
| COMPLETED | 15 | 1 | 1 | 3 | 24 |
| NOT COMPLETED | 8 | 12 | 14 | 10 | 20 |
Baseline Characteristics
| Arm/Group Title | Placebo | PF-06649751 1 mg QD | PF-06649751 3 mg QD | PF-06649751 7 mg QD | PF-06649751 15 mg QD | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | Total of all reporting groups |
| Overall Participants | 23 | 13 | 15 | 13 | 44 | 108 |
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
66.04
(8.79)
|
66.92
(8.79)
|
63.80
(7.76)
|
67.77
(9.36)
|
63.41
(8.47)
|
64.97
(8.60)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
6
26.1%
|
6
46.2%
|
6
40%
|
4
30.8%
|
18
40.9%
|
40
37%
|
| Male |
17
73.9%
|
7
53.8%
|
9
60%
|
9
69.2%
|
26
59.1%
|
68
63%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||
| Hispanic or Latino |
3
13%
|
3
23.1%
|
1
6.7%
|
1
7.7%
|
3
6.8%
|
11
10.2%
|
| Not Hispanic or Latino |
20
87%
|
10
76.9%
|
13
86.7%
|
12
92.3%
|
40
90.9%
|
95
88%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
1
6.7%
|
0
0%
|
1
2.3%
|
2
1.9%
|
| Race (NIH/OMB) (Count of Participants) | ||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
1
7.7%
|
0
0%
|
1
0.9%
|
| Asian |
1
4.3%
|
0
0%
|
2
13.3%
|
1
7.7%
|
6
13.6%
|
10
9.3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
2
8.7%
|
1
7.7%
|
0
0%
|
2
15.4%
|
1
2.3%
|
6
5.6%
|
| White |
20
87%
|
12
92.3%
|
12
80%
|
9
69.2%
|
36
81.8%
|
89
82.4%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
1
6.7%
|
0
0%
|
1
2.3%
|
2
1.9%
|
Outcome Measures
| Title | Change From Baseline in Daily OFF Time at Week 10 |
|---|---|
| Description | A paper Hauser diary was utilized to record motor state for half-hour intervals. Participants completed the diary by answering whether they had been OFF for 3 consecutive days in the week prior to each visit (except Day 28 visit), including 3 consecutive days during the week prior to Day 0 (Randomization). The daily OFF time was calculated as the average of the 3 consecutive daily OFF hours from the Hauser diary at each visit. |
| Time Frame | Week 10; Baseline was defined as the average daily OFF time (using 3 Hauser patient diary days) prior to Day -1 (study derived day and equalled to nominal visit day 0). |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set consisted of all participants randomized who completed at least 1 post-dose efficacy measurement (Hauser home diary). |
| Arm/Group Title | Placebo | PF-06649751 1 mg QD | PF-06649751 3 mg QD | PF-06649751 7 mg QD | PF-06649751 15 mg QD |
|---|---|---|---|---|---|
| Arm/Group Description | The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. |
| Measure Participants | 21 | 7 | 9 | 9 | 41 |
| Least Squares Mean (Standard Error) [Hours] |
-0.969
(0.4092)
|
-1.173
(0.3482)
|
-1.316
(0.3289)
|
-1.480
(0.3460)
|
-1.663
(0.4297)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, PF-06649751 15 mg QD |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Bayesian Dose Response Analysis | |
| Statistical Test of Hypothesis | p-Value | 0.5776 |
| Comments | Bayesian Predictive Test for Emax (the additive increase over Placebo in the response of PF-06649751 at a theoretically infinite dose) Monotonicity | |
| Method | Bayesian Dose Response Analysis | |
| Comments | Estimate and 90% credible interval of Bayesian dose response difference from placebo | |
| Method of Estimation | Estimation Parameter | Bayesian Dose Reponse Estimate |
| Estimated Value | -0.693 | |
| Confidence Interval |
(2-Sided) 90% -1.713 to 0.304 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.6162 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Daily OFF Time |
|---|---|
| Description | A paper Hauser diary was utilized to record motor state for half hour intervals. Participants completed the diary by answering whether they had been OFF for 3 consecutive days in the week prior to each visit (except Day 28 visit), including 3 consecutive days during the week prior to Day 0 (Randomization). The daily OFF time was calculated as the average of the 3 consecutive daily OFF hours from the Hauser diary at each visit. Results at Week 15 should be interpreted with caution given almost half the participants were not available for this analysis at Week 15 as compared to Week 10 and the complicated nature of protocol changes that impacted the study design after Week 10. |
| Time Frame | Weeks 3, 5, 10 and 15; Baseline was defined as the average daily OFF time (using 3 Hauser patient diary days) prior to Day -1 (study derived day and equalled to nominal visit day 0). |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set consisted of all participants randomized who completed at least 1 post-dose efficacy measurement (Hauser home diary). |
| Arm/Group Title | Placebo | PF-06649751 1 mg QD | PF-06649751 3 mg QD | PF-06649751 7 mg QD | PF-06649751 15 mg QD |
|---|---|---|---|---|---|
| Arm/Group Description | The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. |
| Measure Participants | 21 | 7 | 9 | 9 | 41 |
| Change at Week 3 |
-0.67
(0.620)
|
-0.82
(1.237)
|
-0.55
(1.091)
|
-1.82
(1.182)
|
-1.01
(0.464)
|
| Change at Week 5 |
-0.63
(0.490)
|
-2.04
(1.054)
|
-2.23
(0.964)
|
-1.41
(0.937)
|
-1.24
(0.392)
|
| Change at Week 10 |
-0.99
(0.628)
|
-0.60
(1.423)
|
-1.00
(1.508)
|
-2.07
(1.187)
|
-1.63
(0.502)
|
| Change at Week 15 |
1.05
(1.063)
|
-0.67
(2.960)
|
-2.75
(2.936)
|
-1.09
(1.687)
|
-2.47
(0.793)
|
| Title | Change From Baseline in Daily ON Time With Troublesome Dyskinesia |
|---|---|
| Description | A paper Hauser diary was utilized to record motor state for half hour intervals. The participants answered the Hauser diary on whether they had been ON with troublesome dyskinesia. A diary day started with the interval 24:00-0:30 through 23:30-24:00 on each chronological day for 3 consecutive days. On the days recording the home diary, participants made an entry every 30 minutes during their normal waking time and upon awakening from time asleep. The daily ON hours was calculated as the average of the 3 consecutive daily ON hours from the Hauser diary at each visit. Results at Week 15 should be interpreted with caution given almost half the participants were not available for this analysis at Week 15 as compared to Week 10 and the complicated nature of protocol changes that impacted the study design after Week 10. |
| Time Frame | Weeks 3, 5, 10 and 15; Baseline was defined as the average daily ON time with Troublesome Dyskinesia (using 3 Hauser patient diary Days) prior to Day -1 (study derived day and equalled to nominal visit Day 0). |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set consisted of all participants randomized who completed at least 1 post-dose efficacy measurement (Hauser home diary). |
| Arm/Group Title | Placebo | PF-06649751 1 mg QD | PF-06649751 3 mg QD | PF-06649751 7 mg QD | PF-06649751 15 mg QD |
|---|---|---|---|---|---|
| Arm/Group Description | The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. |
| Measure Participants | 21 | 7 | 9 | 9 | 41 |
| Change at Week 3 |
0.17
(0.236)
|
0.07
(0.467)
|
0.19
(0.417)
|
0.01
(0.464)
|
0.23
(0.179)
|
| Change at Week 5 |
0.23
(0.198)
|
-0.21
(0.415)
|
-0.02
(0.388)
|
0.45
(0.363)
|
0.03
(0.162)
|
| Change at Week 10 |
0.13
(0.191)
|
0.24
(0.464)
|
0.32
(0.529)
|
-0.39
(0.389)
|
0.13
(0.167)
|
| Change at Week 15 |
0.01
(0.642)
|
-0.43
(1.349)
|
-0.29
(1.263)
|
0.54
(1.071)
|
-0.21
(0.463)
|
| Title | Change From Baseline in Daily ON Time Without Troublesome Dyskinesia |
|---|---|
| Description | A paper Hauser diary was utilized to record motor state for half hour intervals. The participants answered the Hauser diary on whether they had been ON without troublesome dyskinesia. A diary day started with the interval 24:00-0:30 through 23:30-24:00 on each chronological day for 3 consecutive days. On the days recording the home diary, participants made an entry every 30 minutes during their normal waking time and upon awakening from time asleep. The daily ON hours was calculated as the average of the 3 consecutive daily ON hours from the Hauser diary at each visit. Results at Week 15 should be interpreted with caution given almost half the participants were not available for this analysis at Week 15 as compared to Week 10 and the complicated nature of protocol changes that impacted the study design after Week 10. |
| Time Frame | Weeks 3, 5, 10 and 15; Baseline was defined as the average daily ON time without Troublesome Dyskinesia (using 3 Hauser patient diary days) prior to Day -1 (study derived day and equalled to nominal visit Day 0) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set consisted of all participants randomized who completed at least 1 post-dose efficacy measurement (Hauser home diary). |
| Arm/Group Title | Placebo | PF-06649751 1 mg QD | PF-06649751 3 mg QD | PF-06649751 7 mg QD | PF-06649751 15 mg QD |
|---|---|---|---|---|---|
| Arm/Group Description | The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. |
| Measure Participants | 21 | 7 | 9 | 9 | 41 |
| Change at Week 3 |
0.61
(0.577)
|
1.74
(1.173)
|
-0.49
(1.047)
|
1.93
(1.128)
|
0.77
(0.443)
|
| Change at Week 5 |
0.02
(0.548)
|
2.39
(1.150)
|
1.31
(1.058)
|
1.12
(1.029)
|
1.31
(0.436)
|
| Change at Week 10 |
0.61
(0.618)
|
0.92
(1.413)
|
0.45
(1.598)
|
2.64
(1.194)
|
1.65
(0.508)
|
| Change at Week 15 |
-0.81
(1.099)
|
0.37
(2.999)
|
-4.48
(3.192)
|
0.94
(1.781)
|
1.50
(0.825)
|
| Title | Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III |
|---|---|
| Description | MDS-UPDRS Part III assessed the motor signs of Parkinson's disease and was administered by the investigator. It was comprised of 33 sub-scores based on 18 items, several with right, left or other body distribution scores. Each question was anchored with 5 responses that were linked to commonly accepted clinical terms: 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. If more than 7 of the Part III items were missing, the score for that time point was missing, otherwise MDS-UPDRS Part III score was imputed as sum of the non-missing items*(total number of items)/ (number of items non-missing). The MDS-UPDRS Part III total score range is 0-132. Higher score indicated more severe motor signs of Parkinson's disease. Results at Week 15 should be interpreted with caution given almost half the participants were not available for this analysis at Week 15 as compared to Week 10 and the complicated nature of protocol changes that impacted the study design after Week 10. |
| Time Frame | Weeks 1, 2, 3, 4, 5, 10 and 15; Baseline was defined as the Day -1 (study derived day and equalled to nominal visit Day 0) measurement |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set consisted of all participants randomized who completed at least 1 post-dose efficacy measurement (Hauser home diary). |
| Arm/Group Title | Placebo | PF-06649751 1 mg QD | PF-06649751 3 mg QD | PF-06649751 7 mg QD | PF-06649751 15 mg QD |
|---|---|---|---|---|---|
| Arm/Group Description | The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. |
| Measure Participants | 21 | 7 | 9 | 9 | 41 |
| Change at Week 1 |
-3.90
(2.054)
|
-4.44
(3.965)
|
-4.61
(3.593)
|
-1.90
(3.594)
|
-3.22
(1.524)
|
| Change at Week 2 |
-0.95
(2.078)
|
-15.78
(6.252)
|
0.56
(6.129)
|
-3.70
(1.584)
|
|
| Change at Week 3 |
-3.80
(2.848)
|
-12.39
(8.240)
|
-3.06
(2.069)
|
||
| Change at Week 4 |
-6.28
(2.182)
|
-0.84
(3.940)
|
-2.48
(3.572)
|
-2.91
(3.575)
|
-6.05
(1.574)
|
| Change at Week 5 |
-5.12
(2.386)
|
-6.14
(4.414)
|
3.10
(4.347)
|
-1.22
(3.935)
|
-4.86
(1.765)
|
| Change at Week 10 |
-5.09
(1.967)
|
-2.21
(3.902)
|
5.77
(5.365)
|
-2.36
(3.607)
|
-9.32
(1.526)
|
| Change at Week 15 |
-0.18
(3.170)
|
7.72
(8.660)
|
2.09
(9.495)
|
-5.44
(5.364)
|
-1.84
(2.519)
|
| Title | Change From Baseline in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I, II, IV, and Total Score |
|---|---|
| Description | Each question of Part I,II or IV with 5 responses was linked to the same clinical terms as Part III.The score was missing if more than 7 items were missing for a time point; otherwise Part I,II or IV score was imputed as sum of non-missing items*(total number of items)/(number of items non-missing).•PartI (Non-Motor Aspects of Experiences of Daily Living) assessed non-motor experiences of daily living using 13questions(Range:0-52).•PartII(Motor Aspects of Experiences of Daily Living) assessed motor experiences of daily living using 13questions(Range:0-52).•PartIV(Motor Complications) assessed motor complications,dyskinesias, and motor fluctuations using historical and objective information with 6questions(Range:0-24).•MDS-UPDRS Total Score:the sum of Parts I,II,III,and IV(Range:0-260).Higher score indicated more severe motor signs of Parkinson's disease.Week15's results were interpreted cautiously given almost half participants were not available for the analysis as compared to Week10 |
| Time Frame | Weeks 5, 10 and 15; Baseline was defined as the Day -1 (study derived day and equalled to nominal visit Day 0) measurement |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set included all participants randomized who completed at least 1 postdose efficacy measurement(Hauser home diary). |
| Arm/Group Title | Placebo | PF-06649751 1 mg QD | PF-06649751 3 mg QD | PF-06649751 7 mg QD | PF-06649751 15 mg QD |
|---|---|---|---|---|---|
| Arm/Group Description | The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. |
| Measure Participants | 21 | 7 | 9 | 9 | 41 |
| Change at Week 5 (Part I Score) |
-0.75
(5.508)
|
-0.83
(1.941)
|
0.67
(4.885)
|
2.00
(4.408)
|
1.12
(4.879)
|
| Change at Week 10 (Part I Score) |
-0.69
(4.557)
|
-0.80
(2.168)
|
-1.00
(2.828)
|
0.00
(2.449)
|
0.17
(4.086)
|
| Change at Week 15 (Part I Score) |
-2.86
(6.176)
|
2.00
(NA)
|
6.00
(NA)
|
-1.00
(1.732)
|
1.00
(5.745)
|
| Change at Week 5 (Part II Score) |
0.06
(5.836)
|
-1.83
(2.639)
|
3.00
(4.940)
|
-0.03
(3.083)
|
-0.24
(4.068)
|
| Change at Week 10 (Part II Score) |
-0.35
(5.267)
|
-1.00
(1.225)
|
5.00
(1.414)
|
0.13
(2.428)
|
-0.43
(4.240)
|
| Change at Week 15 (Part II Score) |
-1.38
(4.779)
|
2.00
(NA)
|
8.00
(NA)
|
-2.42
(5.270)
|
1.47
(5.986)
|
| Change at Week 5 (Part IV Score) |
-1.50
(2.895)
|
-0.83
(2.401)
|
-0.50
(4.848)
|
0.25
(2.053)
|
-0.65
(2.806)
|
| Change at Week 10 (Part IV Score) |
-2.00
(2.318)
|
0.80
(1.304)
|
-3.00
(5.657)
|
0.00
(1.789)
|
-1.13
(3.530)
|
| Change at Week 15 (Part IV Score) |
-2.75
(2.493)
|
-2.00
(NA)
|
-7.00
(NA)
|
-1.33
(2.082)
|
-1.27
(2.404)
|
| Change at Week 5 (Total Score) |
-8.88
(12.832)
|
-10.00
(7.616)
|
5.33
(16.860)
|
2.34
(12.010)
|
-4.21
(18.216)
|
| Change at Week 10 (Total Score) |
-8.75
(10.951)
|
-3.60
(8.649)
|
6.50
(7.778)
|
0.13
(10.569)
|
-11.40
(18.448)
|
| Change at Week 15 (Total Score) |
-7.86
(12.456)
|
0.00
(NA)
|
13.00
(NA)
|
-9.08
(13.135)
|
0.73
(17.260)
|
| Title | Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality |
|---|---|
| Description | The safety laboratory tests including Hematology, Clinical Chemistry and Urinalysis were performed. Determination if there were any laboratory data abnormalities of potential clinical concern was based on Pfizer Data Standards. Incidence of laboratory test abnormalities (without regard to baseline abnormality) was summarized within each treatment group. |
| Time Frame | Baseline (Day 0) to Week 17 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set included all participants who received at least 1 dose of PF-06649751 or placebo. |
| Arm/Group Title | Placebo | PF-06649751 1 mg QD | PF-06649751 3 mg QD | PF-06649751 7 mg QD | PF-06649751 15 mg QD |
|---|---|---|---|---|---|
| Arm/Group Description | The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. |
| Measure Participants | 23 | 12 | 15 | 13 | 44 |
| Count of Participants [Participants] |
19
82.6%
|
4
30.8%
|
9
60%
|
7
53.8%
|
25
56.8%
|
| Title | Number of Participants With Vital Sign Results Meeting the Criteria for Categorical Summarization |
|---|---|
| Description | Vital Signs including blood pressure and pulse rate were measured. Vital signs were collected first while the participant was in the supine position and then in the standing position. |
| Time Frame | Baseline (Day 0) to Week 17 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set included all participants who received at least 1 dose of PF-06649751 or placebo and had evaluable data at specified categories. |
| Arm/Group Title | Placebo | PF-06649751 1 mg QD | PF-06649751 3 mg QD | PF-06649751 7 mg QD | PF-06649751 15 mg QD |
|---|---|---|---|---|---|
| Arm/Group Description | The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. |
| Measure Participants | 23 | 13 | 15 | 13 | 44 |
| <90 mmHg (Supine Systolic Blood Pressure [SBP]) |
1
4.3%
|
1
7.7%
|
2
13.3%
|
0
0%
|
3
6.8%
|
| Max-Increase from Baseline >= 30 mmHg (Supine SBP) |
4
17.4%
|
1
7.7%
|
2
13.3%
|
1
7.7%
|
3
6.8%
|
| Max-Decrease from Baseline >= 30 mmHg (Supine SBP) |
4
17.4%
|
1
7.7%
|
2
13.3%
|
2
15.4%
|
11
25%
|
| <90 mmHg (Standing SBP) |
4
17.4%
|
1
7.7%
|
3
20%
|
2
15.4%
|
7
15.9%
|
| Max-Increase from Baseline >=30mmHg (Standing SBP) |
4
17.4%
|
0
0%
|
3
20%
|
1
7.7%
|
3
6.8%
|
| Max-Decrease from Baseline >=30mmHg (Standing SBP) |
3
13%
|
0
0%
|
3
20%
|
2
15.4%
|
12
27.3%
|
| <50 mmHg (Supine Diastolic Blood Pressure [DBP]) |
0
0%
|
0
0%
|
0
0%
|
1
7.7%
|
1
2.3%
|
| Max-Increase from Baseline >=20 mmHg (Supine DBP) |
1
4.3%
|
0
0%
|
0
0%
|
1
7.7%
|
3
6.8%
|
| Max-Decrease from Baseline >=20 mmHg (Supine DBP) |
1
4.3%
|
0
0%
|
2
13.3%
|
1
7.7%
|
13
29.5%
|
| <50 mmHg (Standing DBP) |
2
8.7%
|
0
0%
|
1
6.7%
|
2
15.4%
|
1
2.3%
|
| Max-Increase from Baseline >=20mmHg (Standing DBP) |
3
13%
|
0
0%
|
2
13.3%
|
0
0%
|
1
2.3%
|
| Max-Decrease from Baseline >=20mmHg (Standing DBP) |
5
21.7%
|
2
15.4%
|
3
20%
|
2
15.4%
|
17
38.6%
|
| <40 beats per minute (bpm) (Supine Pulse Rate) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| >120 bpm (Supine Pulse Rate) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| <40 bpm (Standing Pulse Rate) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| >140 bpm (Standing Pulse Rate) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Electrocardiogram (ECG) Results Meeting the Criteria for Categorical Summarization |
|---|---|
| Description | The average of the triplicate readings of ECG data was collected at each assessment time. Number of participants with ECG results meeting the criteria for categorical summarization for time from the beginning of the P wave until the beginning of the QRS complex (PR Interval), time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS Duration), time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT Interval) and corrected QT (Fridericia correction) (QTcF Interval) were presented. |
| Time Frame | Baseline (Day 0) to Week 17 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set included all participants who received at least 1 dose of PF-06649751 or placebo and had evaluable data at specified categories. |
| Arm/Group Title | Placebo | PF-06649751 1 mg QD | PF-06649751 3 mg QD | PF-06649751 7 mg QD | PF-06649751 15 mg QD |
|---|---|---|---|---|---|
| Arm/Group Description | The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. |
| Measure Participants | 23 | 12 | 15 | 13 | 44 |
| >=300 msec (PR Interval) |
1
4.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Max-Increase From Baseline(%)>=25/50%(PR Interval) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| >=140 msec (QRS Duration) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Max-Increase From Baseline(%)>=50% (QRS Duration) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| >=500 msec (QT Interval) |
1
4.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| 450 - <480 msec (QTcF Interval) |
2
8.7%
|
0
0%
|
0
0%
|
0
0%
|
1
2.3%
|
| 480 - <500 msec (QTcF Interval) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| >=500 msec (QTcF Interval) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Max-Increase From Baseline 30-<60 (QTcF Interval) |
1
4.3%
|
0
0%
|
0
0%
|
0
0%
|
1
2.3%
|
| Max-Increase From Baseline >=60 (QTcF Interval) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Suicidal Ideation Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) at Post-baseline Visits |
|---|---|
| Description | The Columbia Suicide Severity Rating Scale (C-SSRS) was an interview based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS responses were mapped to the C-CASA. There were 3 key endpoints for suicidality data analysis and evaluation: Suicidal Behavior: A participant was said to have suicidal behavior if the participant had experienced completed suicide / suicide attempt / reparatory acts toward imminent suicidal behavior. Suicidal Ideation: Any observed suicidal ideation mapped to a single C-CASA category. Suicidal Behavior or Ideation (participants with new onset suicidality): A participant was considered to have a new onset of suicidality if the participant reported no ideation and no behavior at the baseline assessment and reported any behavior or ideation post-baseline. Data observed at screening was not considered in the definition of worsening. |
| Time Frame | Days 0 (Baseline), 7, 14, 21, 28, 35, 70, 77, 84, 91, 105 and 119 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set included all participants who received at least 1 dose of PF-06649751 or placebo and had evaluable data at specified time points. |
| Arm/Group Title | Placebo | PF-06649751 1 mg QD | PF-06649751 3 mg QD | PF-06649751 7 mg QD | PF-06649751 15 mg QD |
|---|---|---|---|---|---|
| Arm/Group Description | The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. |
| Measure Participants | 23 | 13 | 15 | 13 | 44 |
| Baseline |
1
4.3%
|
0
0%
|
1
6.7%
|
0
0%
|
0
0%
|
| Day 7 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Day 14 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
2.3%
|
| Day 21 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
4.5%
|
| Day 28 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Day 35 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
2.3%
|
| Day 70 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Day 77 |
0
0%
|
0
0%
|
|||
| Day 84 |
0
0%
|
0
0%
|
|||
| Day 91 |
0
0%
|
0
0%
|
|||
| Day 105 |
0
0%
|
0
0%
|
0
0%
|
1
7.7%
|
0
0%
|
| Day 119 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Change From Baseline in Total Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease - Rating Scale (QUIP-RS) |
|---|---|
| Description | The QUIP-RS was a brief, patient reported outcome measure designed to assess the severity of symptoms of Impulsive-Compulsive Disorders (ICDs) and related behaviors reported to occur in Parkinson's disease. The QUIP-RS assessed 7 disorders (Gambling, Sex, Buying, Eating, Hobbyism-punding [performing tasks and repeating activities] and Taking medications). If more than 5 items were missing, the total QUIP-RS score was set as missing; otherwise, the total QUIP-RS score was imputed as follows: sum of the non-missing item scores * (total number of items) / (number of items non-missing). The higher score indicated a greater level of the ICD. The total QUIP-RS score for all ICDs and related disorders combined ranges from 0 to 112. |
| Time Frame | Baseline (Day 0) and Weeks 5, 10 and 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set included all participants who received at least 1 dose of PF-06649751 or placebo and had evaluable data at specified time points. |
| Arm/Group Title | Placebo | PF-06649751 1 mg QD | PF-06649751 3 mg QD | PF-06649751 7 mg QD | PF-06649751 15 mg QD |
|---|---|---|---|---|---|
| Arm/Group Description | The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. |
| Measure Participants | 23 | 13 | 15 | 13 | 44 |
| Baseline |
17.1
(16.98)
|
9.0
(12.56)
|
9.0
(14.39)
|
12.5
(11.69)
|
6.8
(11.40)
|
| Change at Week 5 |
-5.6
(11.37)
|
2.3
(10.05)
|
4.7
(9.58)
|
-5.4
(12.28)
|
0.5
(11.13)
|
| Change at Week 10 |
-3.3
(12.16)
|
-1.8
(7.98)
|
-6.5
(9.63)
|
-5.8
(13.50)
|
1.0
(10.62)
|
| Change at Week 15 |
-11.5
(16.29)
|
3.0
(10.30)
|
-3.3
(5.77)
|
-17.0
(11.34)
|
0.4
(5.91)
|
| Title | Total Physician Withdrawal Checklist (PWC-20) on Days 105 and 119, and Change From Day 105 to Day 119 |
|---|---|
| Description | The PWC-20 is a physician completed, 20 item reliable and sensitive instrument for the assessment of discontinuation symptoms. The PWC-20 was collected after the completion of study treatment and also at the first visit of follow-up. The total PWC-20 score was the sum of 20 item scores and ranged from 0 to 60. If more than 5 items were missing, the total PWC-20 score was missing; otherwise, the total PWC-20 score was imputed as follows: sum of the non-missing items * (total number of items) / (number of items non-missing). The higher score indicated more frequent/severe symptoms. |
| Time Frame | Days 105 and 119 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set included all participants who received at least 1 dose of PF-06649751 or placebo and had evaluable data at specified time points. |
| Arm/Group Title | Placebo | PF-06649751 1 mg QD | PF-06649751 3 mg QD | PF-06649751 7 mg QD | PF-06649751 15 mg QD |
|---|---|---|---|---|---|
| Arm/Group Description | The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. |
| Measure Participants | 23 | 13 | 15 | 13 | 44 |
| Day 105 Early Termination (ET) |
3.5
(3.73)
|
5.6
(5.68)
|
5.8
(6.65)
|
8.2
(8.78)
|
7.1
(6.06)
|
| Day 119 Follow-up (FU) |
3.3
(3.08)
|
6.0
(NA)
|
7.7
(4.16)
|
5.8
(5.45)
|
|
| Change From Day 105 ET to Day 119 FU |
-0.6
(3.08)
|
-11.0
(NA)
|
-1.7
(4.73)
|
-0.4
(4.79)
|
| Title | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs and Deaths |
|---|---|
| Description | An AE was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not need necessarily to have a causal relationship with the treatment or usage. An SAE was any untoward medical occurrence at any dose that: Resulted in death; Was life threatening (immediate risk of death); Required inpatient hospitalization or prolongation of existing hospitalization; Resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); Resulted in congenital anomaly/birth defect. |
| Time Frame | Day 1 to follow-up (Week 19 visit) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set included all participants who received at least 1 dose of PF-06649751 or placebo. |
| Arm/Group Title | Placebo | PF-06649751 1 mg QD | PF-06649751 3 mg QD | PF-06649751 7 mg QD | PF-06649751 15 mg QD |
|---|---|---|---|---|---|
| Arm/Group Description | The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. |
| Measure Participants | 23 | 13 | 15 | 13 | 44 |
| AEs |
20
87%
|
7
53.8%
|
11
73.3%
|
10
76.9%
|
37
84.1%
|
| SAEs |
1
4.3%
|
1
7.7%
|
0
0%
|
0
0%
|
2
4.5%
|
| Discontinuation due to AEs |
3
13%
|
1
7.7%
|
3
20%
|
2
15.4%
|
9
20.5%
|
| Death |
1
4.3%
|
0
0%
|
0
0%
|
0
0%
|
1
2.3%
|
Adverse Events
| Time Frame | Day 1 to follow-up (Week 19 visit) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. | |||||||||
| Arm/Group Title | Placebo | PF-06649751 1 mg QD | PF-06649751 3 mg QD | PF-06649751 7 mg QD | PF-06649751 15 mg QD | |||||
| Arm/Group Description | The participants swallowed 3 tablets once daily (QD) at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks. A follow-up visit was at Week 17, 2 weeks after discontinuation of Placebo. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | The participants swallowed 3 tablets QD at approximately the same time each morning within approximately 5 minutes without being manipulated or chewed prior to being swallowed. Duration of treatment was 15 weeks including: 3-week titration of PF-06649751 administered QD to the randomized target dose; 2-week stabilization period for dose adjustment after reaching the target dose; 5-week Period A of PF-06649751 administered QD adjunctive to stable doses of L-Dopa; 5-week Period B (maintenance period) of PF-06649751 administered QD adjunctive to stable doses of L-Dopa. A follow-up visit was at Week 17, 2 weeks after discontinuation of PF-06649751. A follow-up phone visit was scheduled at Week 19 for participant's safety. | |||||
All Cause Mortality |
||||||||||
| Placebo | PF-06649751 1 mg QD | PF-06649751 3 mg QD | PF-06649751 7 mg QD | PF-06649751 15 mg QD | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/23 (4.3%) | 0/13 (0%) | 0/15 (0%) | 0/13 (0%) | 1/44 (2.3%) | |||||
Serious Adverse Events |
||||||||||
| Placebo | PF-06649751 1 mg QD | PF-06649751 3 mg QD | PF-06649751 7 mg QD | PF-06649751 15 mg QD | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/23 (4.3%) | 1/13 (7.7%) | 0/15 (0%) | 0/13 (0%) | 2/44 (4.5%) | |||||
| Gastrointestinal disorders | ||||||||||
| Abdominal pain | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 1/44 (2.3%) | 1 |
| Immune system disorders | ||||||||||
| Allergic oedema | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 1/44 (2.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| Neck pain | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 1/44 (2.3%) | 1 |
| Pain in extremity | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 1/44 (2.3%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Pancreatic carcinoma | 1/23 (4.3%) | 1 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 0/44 (0%) | 0 |
| Renal and urinary disorders | ||||||||||
| Nephrolithiasis | 0/23 (0%) | 0 | 1/13 (7.7%) | 1 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 0/44 (0%) | 0 |
| Ureterolithiasis | 0/23 (0%) | 0 | 1/13 (7.7%) | 1 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 0/44 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||
| Dermatitis allergic | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 1/44 (2.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||||
| Placebo | PF-06649751 1 mg QD | PF-06649751 3 mg QD | PF-06649751 7 mg QD | PF-06649751 15 mg QD | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 15/23 (65.2%) | 7/13 (53.8%) | 11/15 (73.3%) | 10/13 (76.9%) | 31/44 (70.5%) | |||||
| Cardiac disorders | ||||||||||
| Ventricular extrasystoles | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 1/15 (6.7%) | 1 | 0/13 (0%) | 0 | 1/44 (2.3%) | 1 |
| Gastrointestinal disorders | ||||||||||
| Abdominal pain | 1/23 (4.3%) | 1 | 1/13 (7.7%) | 1 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 0/44 (0%) | 0 |
| Constipation | 1/23 (4.3%) | 1 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 | 1/44 (2.3%) | 1 |
| Diarrhoea | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 | 1/44 (2.3%) | 1 |
| Dysphagia | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 | 0/44 (0%) | 0 |
| Flatulence | 0/23 (0%) | 0 | 1/13 (7.7%) | 1 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 0/44 (0%) | 0 |
| Gastrooesophageal reflux disease | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 3/44 (6.8%) | 3 |
| Nausea | 1/23 (4.3%) | 1 | 2/13 (15.4%) | 2 | 2/15 (13.3%) | 2 | 1/13 (7.7%) | 1 | 11/44 (25%) | 14 |
| Vomiting | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 1/15 (6.7%) | 1 | 0/13 (0%) | 0 | 2/44 (4.5%) | 2 |
| General disorders | ||||||||||
| Asthenia | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 1/15 (6.7%) | 1 | 0/13 (0%) | 0 | 1/44 (2.3%) | 1 |
| Fatigue | 3/23 (13%) | 3 | 1/13 (7.7%) | 1 | 2/15 (13.3%) | 2 | 2/13 (15.4%) | 2 | 1/44 (2.3%) | 1 |
| Malaise | 0/23 (0%) | 0 | 1/13 (7.7%) | 1 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 0/44 (0%) | 0 |
| Pyrexia | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 | 0/44 (0%) | 0 |
| Infections and infestations | ||||||||||
| Asymptomatic bacteriuria | 0/23 (0%) | 0 | 1/13 (7.7%) | 1 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 0/44 (0%) | 0 |
| Chronic sinusitis | 0/23 (0%) | 0 | 1/13 (7.7%) | 1 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 0/44 (0%) | 0 |
| Nasopharyngitis | 3/23 (13%) | 4 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 0/44 (0%) | 0 |
| Tooth abscess | 1/23 (4.3%) | 1 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 | 0/44 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||
| Bone contusion | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 | 0/44 (0%) | 0 |
| Contusion | 0/23 (0%) | 0 | 1/13 (7.7%) | 1 | 0/15 (0%) | 0 | 2/13 (15.4%) | 3 | 0/44 (0%) | 0 |
| Fall | 2/23 (8.7%) | 2 | 2/13 (15.4%) | 2 | 1/15 (6.7%) | 1 | 2/13 (15.4%) | 2 | 2/44 (4.5%) | 3 |
| Joint injury | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 1/15 (6.7%) | 1 | 0/13 (0%) | 0 | 0/44 (0%) | 0 |
| Laceration | 0/23 (0%) | 0 | 1/13 (7.7%) | 1 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 1/44 (2.3%) | 1 |
| Skin abrasion | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 | 1/44 (2.3%) | 1 |
| Investigations | ||||||||||
| Blood pressure decreased | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 | 0/44 (0%) | 0 |
| Urine output decreased | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 | 0/44 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||
| Decreased appetite | 1/23 (4.3%) | 1 | 1/13 (7.7%) | 1 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 | 3/44 (6.8%) | 3 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| Flank pain | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 | 0/44 (0%) | 0 |
| Musculoskeletal pain | 0/23 (0%) | 0 | 1/13 (7.7%) | 2 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 1/44 (2.3%) | 1 |
| Musculoskeletal stiffness | 0/23 (0%) | 0 | 1/13 (7.7%) | 1 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 1/44 (2.3%) | 1 |
| Neck pain | 0/23 (0%) | 0 | 1/13 (7.7%) | 2 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 0/44 (0%) | 0 |
| Pain in extremity | 1/23 (4.3%) | 1 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 | 0/44 (0%) | 0 |
| Posture abnormal | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 | 0/44 (0%) | 0 |
| Nervous system disorders | ||||||||||
| Balance disorder | 1/23 (4.3%) | 1 | 0/13 (0%) | 0 | 1/15 (6.7%) | 1 | 1/13 (7.7%) | 1 | 0/44 (0%) | 0 |
| Dizziness | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 1/15 (6.7%) | 1 | 2/13 (15.4%) | 2 | 4/44 (9.1%) | 4 |
| Dyskinesia | 2/23 (8.7%) | 2 | 1/13 (7.7%) | 2 | 1/15 (6.7%) | 1 | 3/13 (23.1%) | 3 | 7/44 (15.9%) | 7 |
| Dystonia | 2/23 (8.7%) | 3 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 1/44 (2.3%) | 1 |
| Headache | 0/23 (0%) | 0 | 2/13 (15.4%) | 2 | 1/15 (6.7%) | 1 | 3/13 (23.1%) | 3 | 11/44 (25%) | 14 |
| Memory impairment | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 | 1/44 (2.3%) | 1 |
| Myoclonus | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 1/15 (6.7%) | 1 | 0/13 (0%) | 0 | 0/44 (0%) | 0 |
| Neuropathy peripheral | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 1/15 (6.7%) | 1 | 0/13 (0%) | 0 | 1/44 (2.3%) | 1 |
| Parkinson's disease | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 1/15 (6.7%) | 1 | 0/13 (0%) | 0 | 1/44 (2.3%) | 1 |
| Somnolence | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 1/15 (6.7%) | 1 | 1/13 (7.7%) | 1 | 0/44 (0%) | 0 |
| Psychiatric disorders | ||||||||||
| Abnormal dreams | 1/23 (4.3%) | 1 | 1/13 (7.7%) | 1 | 1/15 (6.7%) | 1 | 0/13 (0%) | 0 | 3/44 (6.8%) | 4 |
| Aggression | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 | 0/44 (0%) | 0 |
| Anxiety | 1/23 (4.3%) | 1 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 3/44 (6.8%) | 3 |
| Delusion | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 | 0/44 (0%) | 0 |
| Depersonalisation/derealisation disorder | 0/23 (0%) | 0 | 1/13 (7.7%) | 1 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 1/44 (2.3%) | 1 |
| Depression | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 1/15 (6.7%) | 1 | 1/13 (7.7%) | 1 | 1/44 (2.3%) | 1 |
| Dysphemia | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 | 0/44 (0%) | 0 |
| Hallucination | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 | 0/44 (0%) | 0 |
| Hypersexuality | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 1/15 (6.7%) | 1 | 0/13 (0%) | 0 | 0/44 (0%) | 0 |
| Insomnia | 3/23 (13%) | 3 | 1/13 (7.7%) | 1 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 | 2/44 (4.5%) | 2 |
| Irritability | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 4/44 (9.1%) | 4 |
| Rapid eye movement sleep behaviour disorder | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 | 0/44 (0%) | 0 |
| Sleep disorder | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 1/15 (6.7%) | 1 | 1/13 (7.7%) | 1 | 1/44 (2.3%) | 2 |
| Renal and urinary disorders | ||||||||||
| Nephrolithiasis | 0/23 (0%) | 0 | 1/13 (7.7%) | 1 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 0/44 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Dysphonia | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 | 0/44 (0%) | 0 |
| Vascular disorders | ||||||||||
| Flushing | 0/23 (0%) | 0 | 1/13 (7.7%) | 1 | 0/15 (0%) | 0 | 0/13 (0%) | 0 | 0/44 (0%) | 0 |
| Hot flush | 1/23 (4.3%) | 1 | 0/13 (0%) | 0 | 0/15 (0%) | 0 | 1/13 (7.7%) | 1 | 1/44 (2.3%) | 1 |
| Hypertension | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 1/15 (6.7%) | 1 | 0/13 (0%) | 0 | 0/44 (0%) | 0 |
| Hypotension | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 2/15 (13.3%) | 2 | 0/13 (0%) | 0 | 0/44 (0%) | 0 |
| Orthostatic hypotension | 0/23 (0%) | 0 | 0/13 (0%) | 0 | 1/15 (6.7%) | 1 | 0/13 (0%) | 0 | 2/44 (4.5%) | 2 |
Limitations/Caveats
The study was terminated prematurely due to insufficient efficacy and not due to safety reasons.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02687542
Other Study ID Numbers:
- B7601003
- 2015-004912-39
- A-ROSE PD
- A-ROSE
First Posted:
Feb 22, 2016
Last Update Posted:
Nov 23, 2020
Last Verified:
Oct 1, 2020